azithromycin

Azithromycin is used to treat diverse infections, including:

• Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae. A 1999 study found Azithromycin to be faster in resolving symptoms as compared to amoxicillin / clavulanic.{{cite journal|journal=American Journal of Otolaryngology|title=Azithromycin versus amoxicillin/clavulanate in the treatment of acute sinusitis|url=https://www.sciencedirect.com/science/article/abs/pii/S0196070999900443|year=1999|doi=10.1016/S0196-0709(99)90044-3 |pmid=9950107 |access-date=31 May 2024|quote=In adults with acute sinusitis, a 3-day course of azithromycin was as effective and well tolerated as a 10-day course of amoxicillin/clavulanic acid. A significantly simpler dosage regimen and faster clinical effect were the advantages of azithromycin. |volume=20 |issue=1 |pages=7–11 | vauthors = Klapan I, Culig J, Oresković K, Matrapazovski M, Radosević S }}
• Acute otitis media caused by H. influenzae, M. catarrhalis or S. pneumoniae. A 2021 study concluded that Azithromycin was comparable to amoxicillin/clavulanate in its treatment and that it was safer and more tolerable in children.{{cite journal|title=Efficacy and safety of azithromycin and amoxicillin/clavulanate for otitis media in children: a systematic review and meta-analysis of randomized controlled trials|year=2021|doi=10.1186/s12941-021-00434-x |doi-access=free |quote=Azithromycin is comparable to amoxicillin/clavulanate to treat otitis media in children, and it is safer and more tolerable. |journal=Annals of Clinical Microbiology and Antimicrobials |volume=20 | vauthors = Dawit G, Mequanent S, Makonnen E |issue=1 |page=28 |pmid=33894769 |pmc=8070272 }}
• Community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae.{{cite journal | vauthors = Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Musher DM, Niederman MS, Torres A, Whitney CG | title = Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults | journal = Clinical Infectious Diseases | volume = 44 | pages = S27-72 | date = March 2007 | issue = Suppl 2 | pmid = 17278083 | pmc = 7107997 | doi = 10.1086/511159 | doi-access = free | title-link = doi }}
• Genital ulcer disease (chancroid) in men due to H. ducreyi
• Pharyngitis or tonsillitis caused by S. pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy{{cite journal | vauthors = Randel A | title = IDSA Updates Guideline for Managing Group A Streptococcal Pharyngitis | journal = American Family Physician | volume = 88 | issue = 5 | pages = 338–40 | date = September 2013 | pmid = 24010402 }}
• Prevention and treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease due to H. influenzae, M. catarrhalis, or S. pneumoniae. The benefits of long-term prophylaxis must be weighed on a patient-by-patient basis against the risk of cardiovascular and other adverse effects.{{cite journal | vauthors = Taylor SP, Sellers E, Taylor BT | title = Azithromycin for the Prevention of COPD Exacerbations: The Good, Bad, and Ugly | journal = The American Journal of Medicine | volume = 128 | issue = 12 | pages = 1362.e1–6 | date = December 2015 | pmid = 26291905 | doi = 10.1016/j.amjmed.2015.07.032 | doi-access = free | title-link = doi }}
• Trachoma due to C. trachomatis{{cite journal | vauthors = Burton M, Habtamu E, Ho D, Gower EW | title = Interventions for trachoma trichiasis | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD004008 | date = November 2015 | pmid = 26568232 | pmc = 4661324 | doi = 10.1002/14651858.CD004008.pub3 }}
• Uncomplicated skin infections due to S. aureus, S. pyogenes, or S. agalactiae
• Whooping cough caused by B. pertussis.{{cite journal |vauthors=Simon L, Nguyen V |title=Pertussis: The Whooping Cough |journal=Primary Care: Clinics in Office Practice |volume=45 |issue=3 |pages=423–431 |date=September 2018 |pmid=30115332 |doi=10.1016/j.pop.2018.05.003 |title-link = doi }}
• Scrub typhus caused by Orientia tsutsugamushi.{{cite journal |vauthors=Gupta N, Boodman C, Jouego CG, Van Den Broucke S |title=Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis |journal=BMC Infect Dis |volume=23 |issue=1 |pages=884 |date=December 2023 |pmid=38110855 |pmc=10726538 |doi=10.1186/s12879-023-08893-7 | doi-access = free | title-link = doi }}

Azithromycin has relatively broad but shallow antibacterial activity. It inhibits some Gram-positive bacteria, some Gram-negative bacteria, and many atypical bacteria.{{cite journal | doi=10.15557/PiMR.2020.0048 | title=Azithromycin – more than an antibiotic | date=2020 | journal=Pediatria I Medycyna Rodzinna | volume=16 | issue=3 | pages=261–267 | vauthors = Sybilski AJ | doi-access = free | title-link = doi }}{{cite journal |vauthors=Opitz DL, Harthan JS |title=Review of Azithromycin Ophthalmic 1% Solution (AzaSite) for the Treatment of Ocular Infections |journal=Ophthalmol Eye Dis |volume=4 |issue= |pages=1–14 |date=2012 |pmid=23650453 |pmc=3619494 |doi=10.4137/OED.S7791}}{{cite journal |vauthors=Amano A, Kishi N, Koyama H, Matsuzaki K, Matsumoto S, Uchino K, Yamaguchi H, Yokomizo A, Mizuno M |title=In vitro activity of sitafloxacin against atypical bacteria (2009-2014) and comparison between susceptibility of clinical isolates in 2009 and 2012 |journal=Jpn J Antibiot |volume=69 |issue=3 |pages=131–142 |date=September 2016 |pmid=30226949}}

Aerobic and facultative Gram-positive microorganisms

• Staphylococcus aureus (Methicillin-sensitive only)
• Streptococcus agalactiae
• Streptococcus pneumoniae
• Streptococcus pyogenes

Aerobic and facultative anaerobic Gram-negative microorganisms

• Bordetella pertussis
• Haemophilus ducreyi
• Haemophilus influenzae
• Legionella pneumophila
• Moraxella catarrhalis
• Neisseria gonorrhoeae

Anaerobic microorganisms

• Peptostreptococcus species
• Prevotella bivia

Other microorganisms

• Chlamydia trachomatis
• Chlamydophila pneumoniae
• Mycoplasma genitalium
• Mycoplasma pneumoniae
• Ureaplasma urealyticum

While some studies claim that no harm has been found with use during pregnancy, more recent studies with mice during late pregnancy has shown adverse effects on embryonic testicular and neural development of prenatal azithromycin exposure (PAzE) . One recent study claims obvious fetus changes were observed under high-dose, mid-pregnancy and multi-course exposure.{{cite journal | vauthors = Wang H |title=Azithromycin exposure during pregnancy disturbs the fetal development and its characteristic of multi organ toxicity |journal=Elseiver Life Sciences |date=Sep 2023 |volume=329 |doi=10.1016/j.lfs.2023.121985 |pmid=37516432 |url=https://www.sciencedirect.com/science/article/abs/pii/S0024320523006203}} However, there need to be more well-controlled studies in pregnant women.{{cite web | title=Zithromax- azithromycin dihydrate tablet, film coated; Zithromax- azithromycin dihydrate powder, for suspension | website=DailyMed | date=29 September 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b749df83-49b0-433e-8a62-589a048dd716 | access-date=26 April 2024}}

The safety of the medication during breastfeeding is unclear. It was reported that because only low levels are found in breast milk and the medication has also been used in young children, it is unlikely that breastfed infants would have adverse effects.

Azithromycin has beneficial effects in the treatment of asthma. It possesses antibacterial, antiviral, and anti-inflammatory properties which contribute to its effectiveness. Asthma exacerbations can be caused by chronic neutrophilic inflammation, and azithromycin is known to reduce this type of inflammation due to its immunomodulatory properties. The recommended dosage for controlling asthma exacerbations with azithromycin is either 500 mg or 250 mg taken orally as tablets three times a week. In adults with severe asthma, low-dose azithromycin may be prescribed as an add-on treatment when standard therapies such as inhaled corticosteroids or long-acting beta2-agonists are not sufficient. Long-term use of azithromycin in patients with persistent symptomatic asthma aims to decrease the frequency of asthma exacerbations and improve their quality of life. While both its anti-inflammatory and antibacterial effects play crucial roles in treating asthma, studies suggest that responsiveness to azithromycin therapy depends on individual variations in lung bacterial burden and microbial composition, collectively referred to as the lung microbiome. The richness (diversity) of the lung microbiome has been identified as a key factor in determining the effectiveness of azithromycin treatment. Azithromycin has significant interactions with the patient's microbiome. Long-term use of azithromycin reduces the presence of H. influenzae bacteria in the airways but also increases resistance against macrolide antibiotics. The specific pharmacological mechanisms through which azithromycin interacts with the patient's microbiome remain unknown {{as of|2024|lc=y|post=;}} research continues to explore how changes in microbial composition influence drug efficacy and patient outcomes.{{cite journal |vauthors=Chan M, Ghadieh C, Irfan I, Khair E, Padilla N, Rebeiro S, Sidgreaves A, Patravale V, Disouza J, Catanzariti R, Pont L, Williams K, De Rubis G, Mehndiratta S, Dhanasekaran M, Dua K |title=Exploring the influence of the microbiome on the pharmacology of anti-asthmatic drugs |journal=Naunyn-Schmiedeberg's Arch Pharmacol |volume=397 |issue=2 |pages=751–762 |date=February 2024 |pmid=37650889 |pmc=10791706 |doi=10.1007/s00210-023-02681-5 }}

Azithromycin appears to be effective in the treatment of chronic obstructive pulmonary disease through its suppression of inflammatory processes.{{cite journal | vauthors = Simoens S, Laekeman G, Decramer M | title = Preventing COPD exacerbations with macrolides: a review and budget impact analysis | journal = Respiratory Medicine | volume = 107 | issue = 5 | pages = 637–48 | date = May 2013 | pmid = 23352223 | doi = 10.1016/j.rmed.2012.12.019 | doi-access = free | title-link = doi }} Azithromycin is potentially useful in sinusitis via this mechanism.{{cite journal | vauthors = Gotfried MH | title = Macrolides for the treatment of chronic sinusitis, asthma, and COPD | journal = Chest | volume = 125 | issue = 2 Suppl | pages = 52S-60S; quiz 60S-61S | date = February 2004 | pmid = 14872001 | doi = 10.1378/chest.125.2_suppl.52S | url = https://journal.chestnet.org/article/S0012-3692(15)32220-0/fulltext | access-date = 22 March 2020 | archive-date = 27 August 2021 | archive-url = https://web.archive.org/web/20210827234741/https://journal.chestnet.org/article/S0012-3692%2815%2932220-0/fulltext | url-status = live | url-access = subscription }} Azithromycin is believed to produce its effects through suppressing certain immune responses that may contribute to inflammation of the airways.{{cite journal | vauthors = Zarogoulidis P, Papanas N, Kioumis I, Chatzaki E, Maltezos E, Zarogoulidis K | title = Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases | journal = European Journal of Clinical Pharmacology | volume = 68 | issue = 5 | pages = 479–503 | date = May 2012 | pmid = 22105373 | doi = 10.1007/s00228-011-1161-x | s2cid = 1904304 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Steel HC, Theron AJ, Cockeran R, Anderson R, Feldman C | title = Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics | journal = Mediators of Inflammation | volume = 2012 | pages = 584262 | date = 2012 | pmid = 22778497 | pmc = 3388425 | doi = 10.1155/2012/584262 | doi-access = free | title-link = doi }}

Most common adverse effects are diarrhea (5%), nausea (3%), abdominal pain (3%), and vomiting. Fewer than 1% of people stop taking the drug due to side effects. Nervousness, skin reactions, and anaphylaxis have been reported.{{cite journal | vauthors = Mori F, Pecorari L, Pantano S, Rossi ME, Pucci N, De Martino M, Novembre E | title = Azithromycin anaphylaxis in children | journal = International Journal of Immunopathology and Pharmacology | volume = 27 | issue = 1 | pages = 121–6 | date = 2014 | pmid = 24674687 | doi = 10.1177/039463201402700116 | s2cid = 45729751 | doi-access = free | title-link = doi }} Clostridioides difficile infection has been reported with use of azithromycin. Azithromycin does not affect the efficacy of birth control unlike some other antibiotics such as rifampin. Hearing loss has been reported.{{cite book|title=Medical Toxology| vauthors = Dart RC |publisher=Lippincott Williams & Wilkins|year=2004 |pages=23}}

Occasionally, people have developed cholestatic hepatitis or delirium. Accidental intravenous overdose in an infant caused severe heart block, resulting in residual encephalopathy.{{cite journal | vauthors = Tilelli JA, Smith KM, Pettignano R | title = Life-threatening bradyarrhythmia after massive azithromycin overdose | journal = Pharmacotherapy | volume = 26 | issue = 1 | pages = 147–50 | date = January 2006 | pmid = 16506357 | doi = 10.1592/phco.2006.26.1.147 | s2cid = 43222966 }}{{ cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | year = 2008 | pages = 132–133 }}

In 2013, the US Food and Drug Administration (FDA) issued a warning that azithromycin "can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm." The FDA noted in the warning a 2012 study that found the drug may increase the risk of death, especially in those with heart problems, compared with those on other antibiotics such as amoxicillin or no antibiotic. The warning indicated people with preexisting conditions are at particular risk, such as those with abnormalities in the QT interval, low blood levels of potassium or magnesium, a slower than normal heart rate, or those who use certain drugs to treat abnormal heart rhythms.{{cite news |work=The New York Times |title=Popular Antibiotic May Raise Risk of Sudden Death | vauthors = Grady D |date=16 May 2012 |access-date=18 May 2012 |url=https://www.nytimes.com/2012/05/17/health/research/popular-antibiotic-may-raise-risk-of-sudden-death.html |url-status=live |archive-url=https://web.archive.org/web/20120517233434/http://www.nytimes.com//2012/05/17/health/research/popular-antibiotic-may-raise-risk-of-sudden-death.html |archive-date=17 May 2012 }}{{cite journal | vauthors = Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM | title = Azithromycin and the risk of cardiovascular death | journal = The New England Journal of Medicine | volume = 366 | issue = 20 | pages = 1881–90 | date = May 2012 | pmid = 22591294 | pmc = 3374857 | doi = 10.1056/NEJMoa1003833 }}{{cite web|title=FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-azithromycin-zithromax-or-zmax-and-risk-potentially-fatal-heart |publisher=U.S. Food and Drug Administration (FDA) |date=12 March 2013|url-status=live|archive-url=https://web.archive.org/web/20161027222239/https://www.fda.gov/drugs/drugsafety/ucm341822.htm|archive-date=27 October 2016 }} The warning mentioned that azithromycin causes QT prolongation that may cause life-threatening arrhythmias such as torsades de pointes.

Azithromycin, should not be taken with colchicine as it may lead to colchicine toxicity. Symptoms of colchicine toxicity include gastrointestinal upset, fever, myalgia, pancytopenia, and organ failure.{{cite web | url = http://www.hanstenandhorn.com/hh-article05-06.pdf | author1 = John R. Horn | author2 = Philip D. Hansten | title = Life Threatening Colchicine Drug Interactions. Drug Interactions: Insights and Observations | date = 2006 | access-date = 16 January 2024 | archive-date = 23 November 2023 | archive-url = https://web.archive.org/web/20231123052607/http://hanstenandhorn.com/hh-article05-06.pdf | url-status = live }}{{cite journal |vauthors=Tan MS, Gomez-Lumbreras A, Villa-Zapata L, Malone DC |title=Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure |journal=Rheumatol Int |volume=42 |issue=12 |pages=2253–2259 |date=December 2022 |pmid=36104598 |pmc=9473467 |doi=10.1007/s00296-022-05201-5 }}

CYP3A4 is an enzyme that metabolizes many drugs in the liver. Some drugs can inhibit CYP3A4, which means they reduce its activity and increase the blood levels of the drugs that depend on it for elimination. This can lead to adverse effects or drug-drug interactions.{{cite journal |vauthors=Zhang L, Xu X, Badawy S, Ihsan A, Liu Z, Xie C, Wang X, Tao Y |title=A Review: Effects of Macrolides on CYP450 Enzymes |journal=Curr Drug Metab |volume=21 |issue=12 |pages=928–937 |date=2020 |pmid=32807049 |doi=10.2174/1389200221666200817113920 |s2cid=221162650 |url=https://eurekaselect.com/article/download/184894 |access-date=2 February 2024 |archive-date=2 February 2024 |archive-url=https://web.archive.org/web/20240202144113/https://eurekaselect.com/article/download/184894 |url-status=live }}

Azithromycin is a member of macrolides that are a class of antibiotics with a cyclic structure with a lactone ring and sugar moieties. Macrolides can inhibit CYP3A4 by a mechanism called mechanism-based inhibition (MBI), which involves the formation of reactive metabolites that bind covalently and irreversibly to the enzyme, rendering it inactive. Mechanism-based inhibition is more serious and long-lasting than reversible inhibition, as it requires the synthesis of new enzyme molecules to restore the activity.{{cite journal |vauthors=Hougaard Christensen MM, Bruun Haastrup M, Øhlenschlaeger T, Esbech P, Arnspang Pedersen S, Bach Dunvald AC, Bjerregaard Stage T, Pilsgaard Henriksen D, Thestrup Pedersen AJ |title=Interaction potential between clarithromycin and individual statins-A systematic review |journal=Basic Clin Pharmacol Toxicol |volume=126 |issue=4 |pages=307–317 |date=April 2020 |pmid=31628882 |doi=10.1111/bcpt.13343 |url=https://findresearcher.sdu.dk/ws/files/158846448/Interaction_Potential_between_Clarithromycin_and_Individual_Statins_a_Systematic_Review.pdf |access-date=2 February 2024 |archive-date=2 February 2024 |archive-url=https://web.archive.org/web/20240202140200/https://findresearcher.sdu.dk/ws/files/158846448/Interaction_Potential_between_Clarithromycin_and_Individual_Statins_a_Systematic_Review.pdf |url-status=live }}

The degree of mechanism-based inhibition by macrolides depends on the size and structure of their lactone ring. Clarithromycin and erythromycin have a 14-membered lactone ring, which is more prone to demethylation by CYP3A4 and subsequent formation of nitrosoalkenes, the reactive metabolites that cause mechanism-based inhibition. Azithromycin, on the other hand, has a 15-membered lactone ring, which is less susceptible to demethylation and nitrosoalkene formation. Therefore, azithromycin is a weak inhibitor of CYP3A4, while clarithromycin and erythromycin are strong inhibitors which increase the area under the curve (AUC) value of co-administered drugs more than five-fold. AUC it is a measure of the drug exposure in the body over time. By inhibiting CYP3A4, macrolide antibitiotics, such as erythromycin and clarithromycin, but not azithromycin, can significantly increase the AUC of the drugs that depend on it for clearance, which can lead to higher risk of adverse effects or drug-drug interactions. Azithromycin stands apart from other macrolide antibiotics because it is a weak inhibitor of CYP3A4, and does not significantly increase AUC value of co-administered drugs.{{cite journal |vauthors=Westphal JF |title=Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin |journal=Br J Clin Pharmacol |volume=50 |issue=4 |pages=285–95 |date=October 2000 |pmid=11012550 |pmc=2015000 |doi=10.1046/j.1365-2125.2000.00261.x }}

The difference in CYP3A4 inhibition by macrolides has clinical implications, for example for people who take statins, which are cholesterol-lowering drugs that are mainly metabolized by CYP3A4. Co-administration of clarithromycin or erythromycin with statins can increase the risk of statin-induced myopathy, a condition that causes muscle pain and damage. Azithromycin, however, does not significantly affect the pharmacokinetics of statins and is considered a safer alternative than other macrolide antibiotics.

Azithromycin prevents bacteria from growing by interfering with their protein synthesis. It binds to the 50S subunit of the bacterial ribosome, thus inhibiting translation of mRNA. Nucleic acid synthesis is not affected.

Azithromycin is an acid-stable antibiotic, so it can be taken orally with no need of protection from gastric acids. It is readily absorbed, but absorption is greater on an empty stomach. Time to peak concentration (T_max) in adults is 2.1 to 3.2 hours for oral dosage forms. Due to its high concentration in phagocytes, azithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations are released. The concentration of azithromycin in the tissues can be over 50 times higher than in plasma due to ion trapping and its high lipid solubility.{{cite journal | url=http://doi.org/10.1002/bmc.2898 | doi=10.1002/bmc.2898 | title=A concise review of HPLC, LC-MS and LC-MS/MS methods for determination of azithromycin in various biological matrices | date=2013 | journal=Biomedical Chromatography | volume=27 | issue=10 | pages=1243–1258 | pmid=23553351 | vauthors=Sharma K, Mullangi R | access-date=16 February 2024 | archive-date=8 March 2024 | archive-url=https://web.archive.org/web/20240308023320/https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bmc.2898 | url-status=live }}{{cite journal |vauthors=Derendorf H |title=Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin |journal=Int J Antimicrob Agents |volume=55 |issue=6 |pages=106007 |date=June 2020 |pmid=32389720 |pmc=7204663 |doi=10.1016/j.ijantimicag.2020.106007 }} Azithromycin's half-life allows a large single dose to be administered and yet maintain bacteriostatic levels in the infected tissue for several days.

Following a single dose of 500 mg, the apparent terminal elimination half-life of azithromycin is 68 hours. Biliary excretion of azithromycin, predominantly unchanged, is a major route of elimination.{{cite journal | doi=10.5402/2012/859473 | doi-access = free | title-link = doi | title=Application of Different Analytical Techniques and Microbiological Assays for the Analysis of Macrolide Antibiotics from Pharmaceutical Dosage Forms and Biological Matrices | date=2012 | journal=ISRN Analytical Chemistry | volume=2012 | pages=1–17 | vauthors = Bekele LK, Gebeyehu GG }} Over the course of a week, about 6% of the administered dose appears as an unchanged drug in urine.

A team of researchers at the pharmaceutical company Pliva in Zagreb, Croatia discovered azithromycin in 1980.{{cite journal | vauthors = Banić Tomišić Z | title = The Story of Azithromycin | journal = Kemija U Industriji: Časopis Kemičara I Kemijskih Inženjera Hrvatske. | date = December 2011 | volume = 60 | issue = 12 | pages = 603–17 | url = https://www.researchgate.net/publication/286136408 | access-date = 25 June 2020 | archive-date = 8 March 2024 | archive-url = https://web.archive.org/web/20240308023348/https://www.researchgate.net/publication/286136408_The_Story_of_Azithromycin | url-status = live }} The company Pliva patented it in 1981. In 1986, Pliva and Pfizer signed a licensing agreement, which gave Pfizer exclusive rights for the sale of azithromycin in Western Europe and the United States. Pliva put its azithromycin on the market in Central and Eastern Europe. Pfizer launched azithromycin under Pliva's license in other markets under the brand name Zithromax in 1991.{{cite journal| vauthors = Banić Tomišić Z |title=The Story of Azithromycin|journal=Kemija U Industriji|year=2011|volume=60|issue=12|pages=603–617|issn=0022-9830|url=http://pierre.fkit.hr/hdki/kui/en/vol60/abstracts/617.html|url-status=dead|archive-url=https://web.archive.org/web/20170908161922/http://pierre.fkit.hr/hdki/kui/en/vol60/abstracts/617.html|archive-date=8 September 2017|access-date=15 April 2013}} Patent protection ended in 2005.{{cite web|url=https://www.wipo.int/ipadvantage/en/details.jsp?id=906|title=Azithromycin: A world best-selling Antibiotic|website=www.wipo.int|publisher=World Intellectual Property Organization|access-date=18 June 2019|archive-date=6 December 2020|archive-url=https://web.archive.org/web/20201206082124/https://www.wipo.int/ipadvantage/en/details.jsp?id=906|url-status=live}}

File:Zithromax (Azithromycin) tablets.jpg)]]

Azithromycin is available as a generic medication. Azithromycin is administered in film-coated tablet, capsule, oral suspension, intravenous injection, granules for suspension in sachet, and ophthalmic solution.

In 2010, azithromycin was the most prescribed antibiotic for outpatients in the US,{{cite journal | vauthors = Hicks LA, Taylor TH, Hunkler RJ | title = U.S. outpatient antibiotic prescribing, 2010 | journal = The New England Journal of Medicine | volume = 368 | issue = 15 | pages = 1461–2 | date = April 2013 | pmid = 23574140 | doi = 10.1056/NEJMc1212055 | doi-access = free | title-link = doi }} whereas in Sweden, where outpatient antibiotic use is a third as prevalent, macrolides are only on 3% of prescriptions.{{cite journal | vauthors = Hicks LA, Taylor TH, Hunkler RJ | title = More on U.S. outpatient antibiotic prescribing, 2010 | journal = The New England Journal of Medicine | volume = 369 | issue = 12 | pages = 1175–6 | date = September 2013 | pmid = 24047077 | doi = 10.1056/NEJMc1306863 }} In 2017, and 2022, azithromycin was the second most prescribed antibiotic for outpatients in the United States.{{cite web | title=Outpatient Antibiotic Prescriptions — United States, 2017 | website=U.S. Centers for Disease Control and Prevention (CDC) | date=26 March 2020 | url=https://www.cdc.gov/antibiotic-use/community/pdfs/Annual-Report-2017-H.pdf | access-date=30 March 2020 | archive-date=30 March 2020 | archive-url=https://web.archive.org/web/20200330005713/https://www.cdc.gov/antibiotic-use/community/programs-measurement/state-local-activities/outpatient-antibiotic-prescriptions-US-2017.html | url-status=live }}{{cite web | title=Outpatient Antibiotic Prescriptions — United States, 2022 | website=U.S. Centers for Disease Control and Prevention (CDC) | date=15 November 2023 | url=https://www.cdc.gov/antibiotic-use/data/report-2022.html | access-date=17 November 2023 | archive-date=8 March 2024 | archive-url=https://web.archive.org/web/20240308023304/https://www.cdc.gov/antibiotic-use/data/report-2022.html | url-status=live }} In 2022, it was the 78th most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions.

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It is sold under many brand names worldwide including 3-Micina, A Sai Qi, Abacten, Abbott, Acex, Acithroc, Actazith, Agitro, Ai Mi Qi, Amixef, Amizin, Amovin, An Mei Qin, Ao Li Ping, Apotex, Lebanon, Aratro, Aruzilina, Arzomicin, Arzomidol, Asizith, Asomin, Astidal, Astro, Athofix, Athxin, Atizor, Atromizin, Avalon, AZ, AZA, Azacid, Azadose, Azalid, Azalide, AzaSite, Azaroth, Azath, Azatril, Azatril, Azax, Azee, Azeecor, Azeeta, Azelide, Azeltin, Azenil, Azeptin, Azerkym, Azi, Aziact, Azibact, Azibactron, Azibay, Azibect, Azibest, Azibiot, Azibiotic, Azicare, Azicin, Azicine, Aziclass, Azicom, Azicure, Azid, Azidose, Azidraw, Azifam, Azifarm, Azifast, Azifine, Aziflax, Azigen, Azigram, Azigreat, Azikare, Azilide, Azilife, Azilip, Azilup, Azimac, Azimax, Azimed, Azimepha, Azimex, Azimit, Azimix, Azimon, Azimore, Azimycin, Azimycine, Azin, Azindamon, Azinew, Azinex, Azinif, Azinil, Azintra, Aziom, Azipar, Aziped, Aziphar, Azipin, Aziplex, Azipro, Aziprome, Aziquilab, Azirace, Aziram, Aziresp, Aziride, Azirol, Azirom, Azirox, Azirute, Azirutec, Aziset, Azisis, Azison, Azissel, Aziswift, Azit, Azita, Azitam, Azitex, Azith, Azithral, Azithrin, Azithro, Azithrobeta, Azithrocin, Azithrocine, Azithromax, Azithromed, Azithromicina, Azithromycin, Azithromycine, Azithromycinum, Azithrovid, Azitic, Azitive, Azitome, Azitrac, Azitral, Azitrax, Azitredil, Azitrex, Azitrim, Azitrin, Azitrix, Azitro, Azitrobac, Azitrocin, Azitroerre, Azitrogal, Azitrolabsa, Azitrolid, Azitrolit, Azitrom, Azitromac, Azitromax, Azitromek, Azitromicin, Azitromicina, Azitromycin, Azitromycine, Azitrona, Azitropharma, Azitroteg, Azitrox, Azitsa, Azitus, Azivar, Azivirus, Aziwill, Aziwok, Azix, Azizox, Azmycin, Azo, Azobat, Azocin, Azoget, Azoheim, Azoksin, Azom, Azomac, Azomax, Azomex, Azomycin, Azomyne, Azores, Azorox, Azostar, Azot, Azoxin, Azras, Azro, Azrocin, Azrolid, Azromax, Azroplax, Azrosin, Aztin, Aztrin, Aztro, Aztrogecin, Azvig, Azycin, Azycyna, Azydrop, Azypin, Azytact, Azytan, Azyter, Azyter, Azyth, Azywell, Azza, Ba Qi, Bactaway, Bactizith, Bactrazol, Bai Ke De Rui, Batif, Bazyt, Bezanin, Bin Qi, Binozyt, BinQi, Biocine, Biozit, Bo Kang, Canbiox, Cetaxim, Charyn, Chen Yu, Cinalid, Cinetrin, Clamelle, Clearsing, Corzi, Cozith, Cronopen, Curazith, Delzosin, Demquin, Dentazit, Disithrom, Doromax, Doyle, Elzithro, Eniz, Epica, Ethrimax, Ezith, Fabodrox, Fabramicina, Feng Da Qi, Figothrom, Floctil, Flumax, Fu Qi-Hua Yuan, Fu Rui Xin, Fuqixing, Fuxin-Hai Xin Pharm, Geozif, Geozit, Gitro, Goldamycin, Gramac, Gramokil, Hemomicin, Hemomycin, I-Thro, Ilozin, Imexa, Inedol, Infectomycin, Iramicina, Itha, Jin Nuo, Jin Pai Qi, Jinbo, Jun Jie, Jun Wei Qing, Kai Qi, Kang Li Jian, Kang Qi, Katrozax, Ke Lin Da, Ke Yan Li, Koptin, Kuai Yu, L-Thro, Laz, Legar, Lg-Thral, Li Ke Si, Li Li Xing, Li Qi, Li Quan Yu, Lin Bi, Lipuqi, Lipuxin, Lizhu Qile, Loromycin, Lu Jia Kang, Luo Bei Er, Luo Qi, Maazi, Macroazi, Macromax, Macrozit, Maczith, Makromicin, Maxmor, Mazit, Mazitrom, Medimacrol, Meithromax, Mezatrin, Ming Qi Xin, Misultina, Mycinplus, Na Qi, Nadymax, Naxocina, Neblic, Nemezid, Neofarmiz, Nifostin, Nobaxin, Nokar, Novatrex, Novozithron, Novozitron, Nurox, Odaz, Odazyth, Onzet, Oranex, Oranex, Ordipha, Orobiotic, Pai Fen, Pai Fu, Paiqi, Pediazith, Pi Nis, Portex, Pu He, Pu Le Qi, Pu Yang, Qi Gu Mei, Qi Mai Xing, Qi Nuo, Qi Tai, Qi Xian, Qili, Qiyue, Rarpezit, Razimax, Razithro, Rezan, Ribotrex, Ribozith, Ricilina, Rizcin, Romax, Romycin, Rothin (Rakaposhi), Rozalid, Rozith, Ru Shuang Qi, Rui Qi, Rui Qi Lin, Rulide, Sai Jin Sha, Sai Le Xin, Sai Qi, Santroma, Selimax, Sheng Nuo Ling, Shu Luo Kang, Simpli-3, Sisocin, Sitrox, Sohomac, Stromac, Su Shuang, Sumamed, Sumamox, Tailite, Talcilina, Tanezox, Te Li Xin, Tetris, Texis, Thoraxx, Throin, Thromaxin, Tong Tai Qi Li, Topt, Toraseptol, Tremac, Trex, Tri Azit, Triamid, Tridosil, Trimelin, Tritab, Tromiatlas, Tromix, Trozamil, Trozin, Trozocina, Trulimax, Tuoqi, Udox, Ultreon, Ultreon, Vectocilina, Vinzam, Visag, Vizicin, Wei Li Qinga, Wei Lu De, Wei Zong, Weihong, Xerexomair, Xi Le Xin, Xi Mei, Xin Da Kang, Xin Pu Rui, Xithrone, Ya Rui, Yan Sha, Yanic, Yi Nuo Da, Yi Song, Yi Xina, Yin Pei Kang, Yong Qi, You Ni Ke, Yu Qi, Z-3, Z-PAK, Zady, Zaiqi, Zaret, Zarom, Zathrin, Zedbac, Zeelide, Zeemide, Zenith, Zentavion, Zetamac, Zetamax, Zeto, Zetron, Zevlen, Zibramax, Zicho, Zigilex, Zikrax, Zikti, Zimacrol, Zimax, Zimicina, Zimicine, Zindel, Zinfect, Zirom, Zisrocin, Zistic, Zit-Od, Zitab, Zitax, Zithrax, Zithrin, Zithro-Due, Zithrobest, Zithrodose, Zithrogen, Zithrokan, Zithrolide, Zithromax, Zithrome, Zithromed, Zithroplus, Zithrotel, Zithrox, Zithroxyn, Zithtec, Zitinn, Zitmac, Zitraval, Zitrax, Zitrex, Zitric, Zitrim, Zitrobid, Zitrobiotic, Zithrolect, Zitrocin, Zitrogram, Zitrolab, Zitromax, Zitroneo, Zitrotek, Ziyoazi, Zmax, Zocin, Zomax, Zotax, Zycin, and Zythrocin.

It is sold as a combination drug with cefixime as Anex-AZ, Azifine-C, Aziter-C, Brutacef-AZ, Cezee, Fixicom-AZ, Emtax-AZ, Olcefone-AZ, Starfix-AZ, Zeph-AZ, Zicin-CX, and Zifi-AZ.

It is also sold as a combination drug with nimesulide as Zitroflam; in a combination with tinidazole and fluconazole as Trivafluc, and in a combination with ambroxol as Zathrin-AX, Laz-AX and Azro-AM.

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Azithromycin is researched for its supposed anti-inflammatory and immunomodulatory properties, which are believed to be exhibited through its suppression of proinflammatory cytokines and enhancing the production of anti-inflammatory cytokines, which is important in dampening inflammation. Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response. Studies suggest that azithromycin can decrease the release of pro-inflammatory cytokines such as TNF-alpha, IL-1β, IL-6, and IL-8 while increasing the levels of anti-inflammatory cytokine IL-10. By decreasing the number of pro-inflammatory cytokines, azithromycin probably controls potential tissue damage during inflammation. These effects are believed to be due to azithromycin's ability to suppress a transcription factor called nuclear factor-kappa B (NF-κB) resulting in blockade of inflammatory response pathways downstream from NF-κB activation leading to decreased chemokine receptor CXCR4 signaling causing reduced inflammation.{{cite journal |vauthors=Lim DJ, Thompson HM, Walz CR, Ayinala S, Skinner D, Zhang S, Grayson JW, Cho DY, Woodworth BA |title=Azithromycin and ciprofloxacin inhibit interleukin-8 secretion without disrupting human sinonasal epithelial integrity in vitro |journal=Int Forum Allergy Rhinol |volume=11 |issue=2 |pages=136–143 |date=February 2021 |pmid=32725797 |pmc=7854841 |doi=10.1002/alr.22656 }}{{cite journal |vauthors=Yadav S, Dalai P, Gowda S, Nivsarkar M, Agrawal-Rajput R |title=Azithromycin alters Colony Stimulating Factor-1R (CSF-1R) expression and functional output of murine bone marrow-derived macrophages: A novel report |journal=Int Immunopharmacol |volume=123 |issue= |pages=110688 |date=October 2023 |pmid=37499396 |doi=10.1016/j.intimp.2023.110688 |s2cid=260186900 }}{{cite journal |vauthors=Wang Z, Chu C, Ding Y, Li Y, Lu C |title=Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment |journal=J Pediatr (Rio J) |volume= 100|issue= 1|pages= 108–115|date=September 2023 |pmid=37778397 |doi=10.1016/j.jped.2023.06.004 |s2cid=263253426 | doi-access = free | title-link = doi |pmc=10751685 }}{{cite journal |vauthors=Terpstra LC, Altenburg J, Doodeman HJ, ((Piñeros YSS)), Lutter R, ((Heijerman HGM)), Boersma WG |title=The effect of azithromycin on sputum inflammatory markers in bronchiectasis |journal=BMC Pulm Med |volume=23 |issue=1 |pages=151 |date=April 2023 |pmid=37118704 |pmc=10148509 |doi=10.1186/s12890-023-02444-1 | doi-access = free | title-link = doi }}{{cite journal |vauthors=Wu S, Tian X, Mao Q, Peng C |title=Azithromycin attenuates wheezing after pulmonary inflammation through inhibiting histone H3K27me3 hypermethylation mediated by EZH2 |journal=Clin Epigenetics |volume=15 |issue=1 |pages=12 |date=January 2023 |pmid=36691058 |pmc=9872437 |doi=10.1186/s13148-023-01430-y | doi-access = free | title-link = doi }} Despite the efficiency of treating rosacea with azithromycin, the exact mechanism of why azithromycin is effective in treating rosacea are not completely understood.{{cite journal |vauthors=Bakar O, Demirçay Z, Yuksel M, Haklar G, Sanisoglu Y |title=The effect of azithromycin on reactive oxygen species in rosacea |journal=Clin Exp Dermatol |volume=32 |issue=2 |pages=197–200 |date=March 2007 |pmid=17244346 |doi=10.1111/j.1365-2230.2006.02322.x |s2cid=30016695 }} It is unclear whether its antibacterial or immunomodulatory properties or a combination of both mechanisms contribute to its efficacy. Azithromycin may prevent mast cell degranulation and thus can suppress inflammation of dorsal root ganglia through various signaling pathways such as decreased numbers of CD4+ T cells which are particularly relevant since they mediate the response of hair follicle antigens.{{cite journal |vauthors=Ersoy B, Aktan B, Kilic K, Sakat MS, Sipal S |title=The anti-inflammatory effects of erythromycin, clarithromycin, azithromycin and roxithromycin on histamine-induced otitis media with effusion in guinea pigs |journal=J Laryngol Otol |volume=132 |issue=7 |pages=579–583 |date=July 2018 |pmid=29888693 |doi=10.1017/S0022215118000610 |s2cid=47010752 }} Inflammation in rosacea is thought to be associated with increased production of reactive oxygen species (ROS) by inflammatory cells. The ability of azithromycin to decrease ROS production can help reduce oxidative stress and inflammation, but this remains speculation.

The therapeutic role of azithromycin has been explored in various diseases such as cystic fibrosis exacerbation, burn injury-induced lung injury, asthma, chronic obstructive pulmonary disease, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 infection.{{cite journal |vauthors=Durán-Álvarez JC, Prado B, Zanella R, Rodríguez M, Díaz S |title=Wastewater surveillance of pharmaceuticals during the COVID-19 pandemic in Mexico City and the Mezquital Valley: A comprehensive environmental risk assessment |journal=Sci Total Environ |volume=900 |issue= |pages=165886 |date=November 2023 |pmid=37524191 |doi=10.1016/j.scitotenv.2023.165886 |bibcode= 2023ScTEn.90065886D|s2cid=260323001 }}{{cite journal |vauthors=Southern KW, Barker PM |title=Azithromycin for cystic fibrosis |journal=Eur Respir J |volume=24 |issue=5 |pages=834–8 |date=November 2004 |pmid=15516680 |doi=10.1183/09031936.04.00084304 |s2cid=17778741 | doi-access = free | title-link = doi }}{{cite journal |vauthors= |title=Azithromycin and cystic fibrosis |journal=Arch Dis Child |volume=107 |issue=8 |pages=739 |date=August 2022 |pmid=35853636 |doi=10.1136/archdischild-2022-324569 |s2cid=250624603 }}{{cite journal |vauthors=Ghimire JJ, Jat KR, Sankar J, Lodha R, Iyer VK, Gautam H, Sood S, Kabra SK |title=Azithromycin for Poorly Controlled Asthma in Children: A Randomized Controlled Trial |journal=Chest |volume=161 |issue=6 |pages=1456–1464 |date=June 2022 |pmid=35202621 |doi=10.1016/j.chest.2022.02.025 |s2cid=247074537 }}{{cite journal |vauthors=Gibson PG, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, Jenkins C, Peters MJ, Marks GB, Baraket M, Powell H, Taylor SL, ((Leong LEX)), Rogers GB, Simpson JL |title=Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial |journal=Lancet |volume=390 |issue=10095 |pages=659–668 |date=August 2017 |pmid=28687413 |doi=10.1016/S0140-6736(17)31281-3 |s2cid=4523731 }} Despite early evidence showing azithromycin slowed down coronavirus multiplication in laboratory settings, further research indicates it to be ineffective as a treatment for COVID-19 in humans.{{cite journal |journal=Cochrane Database of Systematic Reviews |title=Intervention Antibiotics for the treatment of COVID-19 |vauthors=Popp M, Stegemann M, Riemer M, Metzendorf M, Romero CS, Mikolajewska A, Kranke P, Meybohm P, Skoetz N, Weibel S |date=22 October 2021 |volume=10 |issue=10 |pages=CD015025 |doi=10.1002/14651858.CD015025|pmid=34679203 |pmc=8536098 }} Azithromycin in conjunction with chloroquine or hydroxychloroquine has been associated with deleterious outcomes in COVID-19 patients, including drug-induced QT prolongation.{{cite journal |vauthors=Nag K, Tripura K, Datta A, Karmakar N, Singh M, Singh M, Singal K, Pradhan P |title=Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review |journal=Indian J Community Med |volume=49 |issue=1 |pages=22–27 |date=2024 |pmid=38425958 |pmc=10900474 |doi=10.4103/ijcm.ijcm_983_22 | doi-access = free | title-link = doi }} After a large-scale trial showed no benefit of using azithromycin in treating COVID-19, the UK's National Institute for Health and Care Excellence (NICE) updated its guidance and no longer recommends the medication for COVID-19.{{cite journal | vauthors = Butler CC, Yu LM, Dorward J, Gbinigie O, Hayward G, Saville BR, Van Hecke O, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Djukanovic R, Gadola S, Kirkpatrick J, de Lusignan S, Ogburn E, Evans PH, Thomas NP, Patel MG, Hobbs FD | title = Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial | journal = The Lancet. Respiratory Medicine | volume = 9 | issue = 9 | pages = 1010–1020 | date = September 2021 | pmid = 34329624 | pmc = 8315758 | doi = 10.1016/S2213-2600(21)00310-6 }}{{cite journal |date=31 May 2022 |title=Platform trial rules out treatments for COVID-19 |url=https://evidence.nihr.ac.uk/alert/platform-trial-rules-out-covid-treatments/ |website=National Institute for Health and Care Research (NIHR) |doi=10.3310/nihrevidence_50873 |access-date=1 June 2022 |archive-date=1 June 2022 |archive-url=https://web.archive.org/web/20220601095141/https://evidence.nihr.ac.uk/alert/platform-trial-rules-out-covid-treatments/ |url-status=live |url-access=subscription }}

Azithromycin has been studied in the treatment of chronic fatigue syndrome (CFS) and has been reported to improve or even resolve symptoms in some cases.{{cite journal | vauthors = Klimas NG, Koneru AO | title = Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions | journal = Curr Rheumatol Rep | volume = 9 | issue = 6 | pages = 482–487 | date = December 2007 | pmid = 18177602 | doi = 10.1007/s11926-007-0078-y | url = }}{{cite journal | vauthors = Kavyani B, Lidbury BA, Schloeffel R, Fisher PR, Missailidis D, Annesley SJ, Dehhaghi M, Heng B, Guillemin GJ | title = Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle? | journal = Cell Mol Life Sci | volume = 79 | issue = 8 | pages = 412 | date = July 2022 | pmid = 35821534| pmc = 9276562 | doi = 10.1007/s00018-022-04380-5 | url = }}{{cite journal | vauthors = Van Houdenhove B, Pae CU, Luyten P | title = Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy? | journal = Expert Opin Pharmacother | volume = 11 | issue = 2 | pages = 215–223 | date = February 2010 | pmid = 20088743 | doi = 10.1517/14656560903487744 | url = }}{{cite journal | vauthors = Vermeulen RC, Scholte HR | title = Azithromycin in chronic fatigue syndrome (CFS), an analysis of clinical data | journal = J Transl Med | volume = 4 | issue = | pages = 34 | date = August 2006 | pmid = 16911783 | doi = 10.1186/1479-5876-4-34 | doi-access = free | pmc = 1562448 | url = }}{{cite journal | vauthors = Chia JK, Chia LY | title = Chronic Chlamydia pneumoniae infection: a treatable cause of chronic fatigue syndrome | journal = Clin Infect Dis | volume = 29 | issue = 2 | pages = 452–453 | date = August 1999 | pmid = 10476765 | doi = 10.1086/520239 | url = }} However, these studies have been described as being of very low quality. In any case, the beneficial effects might be by eradication of chronic bacterial infections that are possibly contributing to or causing CFS or by the immunomodulatory effects of azithromycin.

Azithromycin therapy in cystic fibrosis patients yields a modest respiratory function improvement, reduces exacerbation risk, and extends time to exacerbation up to six months; still, long-term efficacy data is a subject of ongoing research. Potential benefits of azithromycin therapy is azithromycin's good safety profile, minimal treatment burden, and cost-effectiveness, but the drawbacks are gastrointestinal side effects with weekly dosing, which are ameliorated by a split dose regimen.{{cite journal |vauthors=Southern KW, Solis-Moya A, Kurz D, Smith S |title=Macrolide antibiotics (including azithromycin) for cystic fibrosis |journal=Cochrane Database Syst Rev |volume=2024 |issue=2 |pages=CD002203 |date=February 2024 |pmid=38411248 |doi=10.1002/14651858.CD002203.pub5 |pmc=10897949 }}{{cite journal |vauthors=Ong JJ, Aguirre I, Unemo M, Kong FY, Fairley CK, Hocking JS, Chow EP, Tieosapjaroen W, Ly J, Chen MY |title=Comparison of gastrointestinal side effects from different doses of azithromycin for the treatment of gonorrhoea |journal=J Antimicrob Chemother |volume=77 |issue=7 |pages=2011–2016 |date=June 2022 |pmid=35411400 |pmc=9244214 |doi=10.1093/jac/dkac118 }} The potential role of azithromycin in inhibiting the autophagic destruction of non-tuberculous mycobacteria (NTM) within macrophages has garnered significant attention. This mechanism may contribute to the observed correlation between long-term macrolide monotherapy and an increased risk of NTM infection and the emergence of macrolide-resistant strains. Azithromycin's interference with autophagy could potentially predispose patients with cystic fibrosis to mycobacterial infections. Despite repeated refutations of a direct association between azithromycin use and NTM infection, there remains a high level of concern regarding the potential for the development of NTM strains resistant to macrolides.{{cite journal |vauthors=Gramegna A, Misuraca S, Lombardi A, Premuda C, Barone I, Ori M, Amati F, Retucci M, Nazzari E, Alicandro G, Ferrarese M, Codecasa L, Bandera A, Aliberti S, Daccò V, Blasi F |title=Treatable traits and challenges in the clinical management of non-tuberculous mycobacteria lung disease in people with cystic fibrosis |journal=Respir Res |volume=24 |issue=1 |pages=316 |date=December 2023 |pmid=38104098 |pmc=10725605 |doi=10.1186/s12931-023-02612-1| doi-access = free | title-link = doi }}

Azithromycin has been shown to be an effective preventive measure against many postpartum infections in mothers following planned vaginal births; still, its impact on neonatal outcomes remains inconclusive and is the subject of ongoing research.{{cite journal |vauthors=Crosara LF, Orsini PV, Eskandar K, Khalil SM, Castilhos GS, Strahl PA, Milbradt TL, Philip CE |title=Single-dose oral azithromycin prophylaxis in planned vaginal delivery for sepsis prevention: A systematic review and meta-analysis of randomized controlled trials |journal=Int J Gynaecol Obstet |volume=165 |issue=1 |pages=107–116 |date=April 2024 |pmid=37724021 |doi=10.1002/ijgo.15124}}{{cite journal |vauthors=Ye H, Hu J, Li B, Yu X, Zheng X |title=Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials |journal=BMC Pregnancy Childbirth |volume=24 |issue=1 |pages=200 |date=March 2024 |pmid=38486177 |pmc=10938810 |doi=10.1186/s12884-024-06390-6 | doi-access = free | title-link = doi }}

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